Many features and behaviors of developing nerve cells are strictly related to their locations in the brain and their positions relative to one another. By means of position-dependent differentiation, the young neuron acquires unique cellular properties which govern its relations with other neurons, its role and position in fiber projections, and its formation of synaptic connections. This proposal offers a comprehensive and interdisciplinary approach to major unresolved questions on the determination and development of neuronal locus specificity in retinal ganglion cells, and the expression of these properties during the assembly of retinotectal connections in frogs and fish. All the experiments employ proven and familiar techniques of cell, developmental, and neural biology to obtain solid information about cellular and subcellular mechanisms. Every proposed experiment has been selected on the basis of the promise offered by results of careful pilot studies. Specifically, we plan to further analyze the early programming events which establish the blueprint for retinotectal patterns, and its relation to morphological differentiation of the first ganglion cells. We also propose to examine in detail the process by which the young ganglion cell acquires positional information. Finally, we propose experiments on the nature and expression of locus specificity, and the mechanisms by which optic fibers interact with one another and with tectal cells during development of retinotectal connections.